[!INFO] Intrinsic Vs. Extrinsic pathways.
In reality, there is some overlap between the pathways.
However,
Intrinsic - meaning all the necessary factors for activation are present in the blood. Also activated when blood comes into contact with glass.
Extrinsic pathway - Some components are not present in the blood. Activated when blood contacts tissue factors released from damaged tissue.
Key points about the coagulation cascade
Sources: beef lung or hog intestine; Same amount of different preparations of heparin will have different activities so dosing is specified in units of activity rather than mass.
Activates antithrombin III.
Use is usually reserved for patients in renal failure.
Enoxaparin and dalteparin are heparin fragments, fondaparinux is a synthetic pentasaccharide. These are all referred to as low molecular weight heparins.
Longer acting than heparin. Contraindicated in renal failure.
Mechanism: While heparin potentiates the action of antithrombin on IIa, LMWH potentiates the action of antithrombin on Xa. Xa inactivation does not require that ATIII and the Xa substrate both be bound to the LMWH molecule.
| Heparin | LMWH |
|---|---|
| 15kDa molecule | 4 kDA molecule |
| Contraindicated in renal failure | |
| Potentiates anti Iia action of antithrombin II | Potentiates anti Xa action of antithrombin III |
| Saturation kinetics at high dose | First order kinetics |
| Longer half life | |
| Titrated against APTT | APTT is insensitive; not usually prolonged with LMWH |
| Given IV (or even sub cut) | Given sub cut |
| Immediate action when given IV | - |
| Inactivated by protamine | - |
| can cause Thrombosis | - |
| Heparin induced thrombocytopenia | - |
| Osteoporosis with chronic treatment | - |
Antibodies are produced against heparin+platelet factor 4.
This is found on platelets and edothelial cells. Circulating immune complexes bind to platelet (thrombocytopaenia) and blood vessels (endothelial damage) and can result in DIC.
~~## vW disease
vWF is made by endothelium.
Roles:
1) Platelet adhesion + aggregation (see [[#Formation of the primary platelet plug]]) -> Intrinsic pathway defect -> Prolonged APTT
2) Transport of factor VIII. -> Low factor VIII levels
Commonest inherited bleeding disorder; usually autosomal dominant.
Mucosal bleeding.
[!INFO] Titrable acid in urine
A measure of the amount of H2PO2 formed as a result of secretion of excess H+ by the tubues.
Titratble acidity refers to the amount of base (eg. NaOH) required to titrate the urine pH back to 7.4 (from it's currently acidic pH).
Titrable acidity measures the amount of 'non HCO3-' absorbers of urinary H+.
i.e Mostly phosphate.
Ammonium is not measured by this method because due to the high pK of ammonium, no H+ is removed from NH4+ during titration to a pH of 7.4.
Ketoanions also constitute titrable acid but only in DKA.
#2022SBR Q22
aka pseudotumour cerebri
Cerebral venous thrombosis presents with very similar features!
Typical history: Woman of childbearing age who is overweight, presents with episodes of severe throbbing headache with papilloedema (bilateral and symmetric) and pulsatile tinnitus.
They can have visual disturbances and diplopia due to abducens nerve palsy.
On presentation, imaging (MRI) is needed to exclude other causes of raised intracranial pressure. In IIH, MRI will show normal brain parenchyma, with no evidence of hydrocephalus, or mass lesions.
Lumbar puncutre is done once MRI excludes another cause for raised ICP.
Opening pressure > 250cmH20 confirms elevated ICP. CSF composition will be normal.
The major morbidity associated with idiopathic intracranial hypertension (IIH) is vision loss.
The visual field loss is typically peripheral with nerve fiber bundle type defects predominating. Central defects occur in more advanced disease.
Exact pathogenesis is unknown.
Known causes: tetracyclines including doxycyline and minocycline. Hypervitaminosis A (excessive dietary intake / retinoic acid, isotretinoin)
Treatment : acetazolamide or other carbonic anhydrase inhibitor ; frusemide can be used as adjunct +/- analgesia.
Refractory disease: surgical treatment : CSF shunting procedure or optic nerve sheath fenestration.
Patients require follow up with ophthalmologic monitoring.
upper left image shows increased cup - disk ratio in glaucoma; not relevant to papilloedema
Oxygen saturation = how much Hb is bound to oxygen compared to how much Hb is unbound.
P50 is the PO2 at which saturation is 50%.
With each O2 molecule that binds to the Hb molecule, the affinity of the Hb for O2 increases. This is what produces the sigmoid shape of the curve.
However, note that increasing PO2 cannot be said to shift the curve to the left!
Factors affecting the Oxygen dissociation curve:
| Left shift (increased affinity) | Right shift (decreased affinity) |
|---|---|
| Incr. Temperature | |
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